Dr Xi Yang heads the world-renowned Department of Immunology at the University of Manitoba, Canada. Here, he discusses how the Department has changed since its foundation in the 1960s, as well as current research and training opportunities

Could you begin by introducing the Department of Immunology at the University of Manitoba?

We have a long history of excellence in research and education. We are the first independent immunology department to be established in Canada. Our founder, Dr Alec Sehon, recruited 35 scientists and trainees, mainly immunologists, from McGill University in Montreal, and moved them and his lab to the Faculty of Medicine at the University of Manitoba in 1969. The establishment of the Department marked the first step towards transplant surgery in Manitoba.

This year marks our 45th anniversary. We have grown significantly since that time, gaining international recognition for our studies in basic immunology, interdisciplinary work and translational immunology, especially in the areas of allergy, transplantation and infectious diseases. Currently, we are one of only two independent immunology departments in Canada and accomodate nearly 100 researchers, including 30 professors, 40 graduate students, research associates and postdoctoral fellows, as well as technical, administrative and support staff. We provide excellent immunology training opportunities for MSc, PhD, BSc and MD/PhD degree students.

How has the Department evolved since it was founded in 1969, and what are the key research foci?

Our teaching and research capacity, as well as the spectrum of research, has expanded significantly since then. Early on, our focus was on immunochemistry and allergy research. We now also research immune regulation in multiple physiological and pathological settings including allergy/asthma, infection and transplantation, as well as chronic inflammation and cancer. As we grew, so did

our needs for lab space. In 1974, we moved to the sixth floor of the new Basic Medical Sciences Building on the Health Sciences Campus. We outgrew our space again, and in 2009 relocated to our brand new facility on the fourth floor of the Apotex Centre. We now conduct research, teaching and administrative activity in an 18,000 square foot space, which includes an open-concept laboratory with state-of-the-art infrastructure.

We have three core research platforms supported by the Faculty of Medicine at the University of Manitoba, and Department members have access to research facilities in the National Microbiology Laboratory of Canada (NML), the Canadian Food Inspection Agency (CFIA), the Manitoba Institute of Child Health (MICH) and the Manitoba Centre for Proteomics and Systems Biology. Our current focus is to improve our multidisciplinary programme in immunology and promote translational research.

What led you to the role of head?

For most of my academic career, I have been an educator and researcher. This involves teaching graduate and undergraduate courses, supervising MSc and PhD students in immunology and medical microbiology and investigating immune mechanisms of allergy and infectious diseases. My research has been continuously supported by the Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation (CFI) and the federal Canada Research Chairs (CRC) programme since I became an independent researcher in 1997.

I have also served as a reviewer on national and international research grant and award review panels, as well as the editor of scientific international journals, gaining national and international recognition along the way. On the service side, I have been a member of the Faculty Council of Graduate

Studies and chair of various departmental committees. This experience in teaching, research and services provided me with the confidence to apply for this job. When the position was posted last year, I felt the timing was right for me to do more for the University and our colleagues. I received strong support and encouragement from colleagues, which was very important to me.

Can you describe what the position entails, and how you effectively balance your commitments?

I have many administrative duties to fulfil. Striking a balance with other duties can be tricky, as it requires a large time commitment, but it is achievable. In general, the Head oversees all teaching and research activities in the Department. The role requires a good understanding of university policies, interpersonal skills and most importantly, a vision for the Department’s future. This is a very challenging job for a researcher and educator like me who is new to this position.

Since my appointment, I have made a great effort to learn and understand university policies, rules and regulations, the teaching curriculum and budget management. I also pay much more attention to our graduate programme, faculty development and facility improvement. I keep an eye out for research funding opportunities for our members, especially new initiatives and team grant opportunities offered by local, national and international agencies. In order to balance administrative tasks and my own research programme, it is important to consider the Department a priority. At the same time, I delegate some of the administrative duties to my colleagues, mainly through departmental committees. I am extremely lucky that the academic members and assistants in our collegial department are very supportive and accommodating, which makes my life much easier.

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Having received international recognition, can you discuss some of the major research to come out of the Department?

Allergy/asthma and transplantation studies are our traditional research strengths. In fact, one of the major reasons for the original establishment of the Department and relocation of Dr Alec Sehon’s group from Montreal to Winnipeg was to join the efforts of transplantation study at the University of Manitoba.

These areas remain our strengths, but a much broader spectrum of cutting-edge research activities are carried out in the Department today, which has generated international recognition in the areas of infection and immunity, immune cell signalling, cancer and chronic inflammation. Four Department members received Canada Research Chair awards and four received Manitoba Research Chair awards. A new GlaxoSmithKline Research Chair is currently being recruited to work on infectious immunology.

What are some of the professional opportunities for advancement on offer?

Our graduate programme has a strong track record of excellence. Formal training in the Department is mainly for MSc and PhD degree students and postdoctoral fellows. Some clinical fellows pursue graduate degrees in immunology in their clinical fellowship training.

The Department also offers training opportunities for advanced degrees (MD/PhD programme) and the Bachelor of Sciences (Medicine) degree for medical students, coordinated by the Faculty of Medicine. The Department also offers summer student and co-op student opportunities and hosts visiting professors from all over the world.

Do you play a role in nurturing the next generation of scientists?

I have my own graduate students who are pursuing MSc and PhD degrees in immunology or medical microbiology, as well as postdoctoral fellows and visiting scholars working in my laboratory. I also have visiting students from the research groups with which I collaborate. As Head of the Department, I make a special effort to improve our graduate programme and the training environment. I regularly attend the weekly journal clubs and research seminars presented by trainees and encourage all faculty members to participate in all of these activities.

The Department offers various types of awards to encourage student excellence in academic performance, presentation skills and research activities. We fund a visiting professor programme in order to give them the opportunity to interact with international authorities in immunology. I enjoy chatting with students about their academic and research concerns and am interested to know about the cultures they come from and hear about their social activities. Our cohort of trainees is strong, active, enthusiastic, committed, supportive and well organised.

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DEPARTMENT OF IMMUNOLOGY, UNIVERSITY OF MANITOBA

THE IMMUNE SYSTEM is a vital but complex system. When it works well, it allows the body to fight infection. However, it sometimes goes awry, underlying a host of medical conditions, including autoimmune diseases such as Type 1 diabetes, inflammatory diseases like arthritis, and even cancer. Understanding the intricacies of the immune system holds the clues to treating these conditions. Dr Xi Yang, Canada Research Chair in Infection and Immunity, has dedicated his career to unravelling the mysteries of immunology. He currently heads the Department of Immunology at the University of Manitoba, a world-renowned centre for research on immunology.

The Department was established in 1969, with five faculty and just eight students, and was the first immunology department in Canada. It has evolved significantly since that time, and today represents a multidisciplinary immunology programme comprising both basic and clinical biomedical scientists, covering a wide range of research areas. The 45-year-old Department is likely the oldest in all of North America and remains one of only two in Canada.

INTERNATIONAL SYNERGY

The Department is recognised for its strength in both research and teaching, supported by excellent research faculty, high-achieving students and cutting-edge facilities. “There are around 30 primary and cross-appointed professors in the Department. In addition to the scientists on site, many immunology laboratories are scattered throughout Winnipeg and the university campus,” Yang explains. These include: the Manitoba Institutes of Child Health, Cell Biology and Proteomics; National Microbiology Laboratory; Health Sciences Centre; Children’s Hospital; and Canadian Blood Services.

Faculty, students and staff come from around the globe to access the unique facilities, as Yang describes: “Our Department is truly international in nature, with trainees coming from all corners of

the world. Moreover, our Department members have established collaborative relationships with institutions in other Canadian provinces, the US, Europe, Asia and Africa”. These international links expand the capacity of the Department and facilitate and accelerate successful research.

STATE-OF-THE-ART FACILITIES

After outgrowing its previous location in the Basic Medical Sciences building, in 2009 the Department moved to the Apotex Centre. The 18,000 square foot Centre is home to an open-concept laboratory with leading-edge facilities for a range of molecular and cellular analyses. Moreover, enabling trainees to work side-by-side with faculty members creates a more integrated research system and facilitates problem solving. The facilities of the Department are funded through competitive grants and it is now home to three of the University’s eight core research platforms: flow cytometry, large-scale RNA and protein analysis for immunological biomarkers in health and disease, and lentiviral vector viral particles production.

TRANSLATIONAL RESEARCH

The Department conducts wide-ranging research, using diverse techniques and approaches, which is supported by high levels of peer-reviewed external funding. This research has important implications for human health, the realisation of which is facilitated by strong partnerships between fundamental and clinical immunology groups. It addresses multiple human diseases including asthma, inflammatory bowel diseases and graft rejection; as well as infectious diseases and cancer. Approaches include gene therapy, stem cell technology, animal models and human cohorts.

BREATHE EASY

One area in which the Department is particularly active is asthma – a major challenge in

immunology. Asthma is a chronic allergic disease, affecting some 235 million people, and is life-threatening in the most severe cases. The Department is home to a node of the Canadian Human Immunology Network, a Canadian Institutes of Health (CIHR)-funded initiative to promote increased basic research in human immunology. Drs Kent HayGlass and Allan Becker have played leading roles in the Canadian Healthy Infant Longitudinal Development (CHILD) study since its foundation in 2008. Involving 5,000 infants, this national longitudinal birth cohort was established to investigate the impact of environmental exposures, genetics and their interactions on the developing foetus and infant, primarily seeking to understand the root causes of allergic disorders and asthma.

At the molecular level, Dr Abdel Soussi Gounni’s laboratory has been focusing on defining the pathways that affect inflammatory cells and airway structural cells in chronic airway diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). In recent years, Soussi Gounni’s research has revealed a critical role of Semaphorin 3E (Sema3E) and acute phase protein pentraxin-3 (PTX3) in inflammation and tissue remodelling using both human clinical samples and animal models. His findings provide in vivo evidence and proof of principle that therapeutic intervention with Sema3E and PTX3 might benefit inflammatory airway disorders such as asthma and COPD.

The Department’s different strands

of translational research and truly

interdisciplinary approach have

received recognition worldwide

A multidisciplinary departmentThe Department of Immunology at the University of Manitoba was the first of its kind in Canada. Today, it is an internationally esteemed centre for immunology research and teaching, offering an outstanding research environment with cutting-edge facilities

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DEPARTMENT OF IMMUNOLOGY, UNIVERSITY OF MANITOBA

DEPARTMENT OF IMMUNOLOGY, UNIVERSITY OF MANITOBA

OBJECTIVES

To continue cutting-edge research activities in infection and immunity, immune cell signalling, cancer and leukaemia, and chronic inflammation.

FUNDING

Canadian Institutes of Health Research (CIHR)

Canada Foundation for Innovation

National Science and Engineering Research Council (NSERC)

Canada Cancer Institute

Manitoba Health Research Council

University of Manitoba

CONTACT

Dr Xi Yang Canada Research Chair in Infection and Immunity and Professor and Head, Department of Immunology

University of Manitoba College of Medicine Faculty of Health Sciences 471 Apotex Centre 750 McDermot Avenue Winnipeg, Manitoba R3E 0T5 Canada

T +1 204 272 3082 E xi.yang@med.umanitoba.ca

http://umanitoba.ca/faculties/medicine/units/immunology/index.html

DR XI YANG obtained his medical degree and MSc degree from Shandong Medical University in China in the 1980s. He then received his PhD degree in Immunology at the University of Manitoba in 1993. Yang became an assistant professor in the Departments of Medical Microbiology and Immunology at the University of Manitoba in 1997 and was promoted to Associate and Full Professor in 2000 and 2005 respectively, and later appointed as Head of the Department of Immunology in 2013. Yang’s current research programme focuses on the cellular and molecular basis of immune responses to allergens and infectious agents and on the development of immunoprophylactic approaches for allergy and infectious diseases.

TRANSPLANT SURVIVAL

Transplantation immunology is another traditional strength of the Department. Transplantation has dramatically extended the life of patients with organ failure, but rejection by the host is a major obstacle. Early identification is critical for intervention, but not easily done. Although biopsy is reliable for observing rejections, it is costly, inconvenient and carries some risk of complications. It is therefore unsuitable for frequent monitoring.

To overcome this restriction, Drs Peter Nickerson and Juliet Ho are developing new urine tests for quick and early monitoring of reject inflammation in the graft kidney and regular follow up. They are using proteomics and systems biology approaches to identify biomarker proteins with rejection diagnostic potential. At the same time, they are studying blood antibodies related to kidney rejection.

Many types of antibodies to different proteins are found in transplant patients but the most relevant ones causing rejection are yet to be identified. The researchers are trying to address this issue and establish novel diagnostic blood tests to detect antibody-mediated rejection prior to them causing the kidney to malfunction or sustain damage. The early detection of urine proteins and blood antibodies may identify the biomarkers, allowing for clinicians to intervene early and thereby improve transplant and patient survival.

SIGNALLING MATTERS

Beyond asthma and transplantation, another major study, led by Dr Aaron Marshall is mapping the signal transduction events that control B cell activation. In collaboration with the Manitoba CLL (chronic lymphocytic lymphoma) Tumour Bank, Marshall’s lab has found that PI3K inhibitors, which block PI3K signalling, effectively block the ability of leukaemic B cells to migrate

and adhere to bone marrow stromal cells – both crucial events promoting CLL accumulation in bone marrow and lymph nodes.

His group is currently working to define the molecules involved in this event. Their work is the first to examine PI-binding proteins including Bam32/DAPP1, TAPP1, TAPP2 and lammelipodin, for their roles linking PI3K to B cell proliferation and migration functions. In addition, they are extensively studying control of the PI3K pathway by lipid phosphatases PTEN, SHIP and INPP4. Alterations in these phosphatases have been linked with inflammatory diseases or cancer.

FIGHTING THE OUTSIDES

Infection and immunity is a new research strength for the Department. Dr Jude Uzonna’s laboratory focuses on basic mechanisms and the development of effective therapies and vaccines against parasitic infections. His work on cutaneous leishmaniasis has strong translational potential. Novel therapeutic targets and vaccine candidates are therefore now on the horizon.

Uzonna’s discoveries are currently protected by two major US patents. The first stems from the researchers’ striking discovery that P13K regulates immunity to Leishmania major. This finding suggests that blocking the PI3K pathway with highly specific pharmacologic inhibitors may offer a potential new therapy for cutaneous leishmaniasis. The second patent involves the identification of novel peptides and proteins that elicit strong protective T cell response in mice and humans using reverse immunology and proteomics approaches.

The Department’s different strands of translational research and truly interdisciplinary approach have received recognition worldwide. Its discoveries are contributing to great progress in immunology and beyond, supported by its excellent facilities, diverse outlook and world-class expertise.

INTELLIGENCE

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